The Development and Failure of Social Norms in Second Life

This Note analyzes the development and efficacy of social norms in maximizing the welfare of participants in the virtual community of Second Life. Although some of these norms developed appropriately in response to the objectives and purposes of this virtual world, Second Life is so thoroughly steeped in conditions that have impeded the development of successful social norms in other communities that any system of social norms in Second Life will ultimately fail. Because social norms will likely,fail to successfully maximize resident welfare, regulatory schemes imposed both by the operators of the virtual world and by real-world governing institutions are needed to enhance the functioning of this particular alternative reality inhabited by millions

hTERT expression in melanocytic lesions: an immunohistochemical study on paraffin-embedded tissue

Telomerase plays a role in the immortalization of cells and carcinogenesis. Previous studies have yielded conflicting results on whether human telomerase RNA (hTER) expression differs in nevi, atypical nevi and melanomas using polymerase chain reaction-based telomeric repeat amplification protocol or in situ hybridization assays. The aim of this study was to evaluate human telomerase reverse transcriptase (hTERT) staining in melanocytic lesions on paraffin-embedded tissues. Methods:  Paraffin-embedded sections from 12 acquired nevi, seven dysplastic nevi, 11 Spitz nevi, eight primary invasive melanomas, and three metastatic melanomas were studied for staining intensity (0–3+) and percentage of labeled cells with anti-hTERT. Results:  hTERT staining was observed in most cells (>75%), in all but three lesions, and was of greater intensity in the nucleus, especially the nucleolus, compared with the cytoplasm. Spitz nevi tended to have weaker hTERT staining (mean = 1.7) compared with acquired nevi (mean = 2.2), dysplastic nevi (mean = 2.4), primary melanomas (mean = 2.4), or metastatic melanomas (mean = 3). Conclusions:  Although telomerase activity was weaker in Spitz nevi, there was overlap with other nevi and primary invasive melanomas in our small series. Thus, hTERT expression does not appear to be a reliable adjunct to the histological diagnosis of primary melanocytic lesions. Fullen DR, Zhu W, Thomas D, Su LD. hTERT expression in melanocytic lesions: an immunohistochemical study on paraffin-embedded tissue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75519/1/j.0303-6987.2005.00403.x.pd

Can lymphangiosarcoma be resurrected? A clinicopathological and immunohistochemical study of lymphatic differentiation in 49 angiosarcomas

Mankey C C, McHugh J B, Thomas D G & Lucas D R (2010) Histopathology 56 , 364–371 Can lymphangiosarcoma be resurrected? A clinicopathological and immunohistochemical study of lymphatic differentiation in 49 angiosarcomas The term lymphangiosarcoma has largely been abandoned in the current classification of endothelial neoplasms. Recently, a number of lymphatic-associated antibodies have been developed for immunohistochemistry, which frequently stain angiosarcomas, implying lymphatic or mixed lymphatic and blood vascular differentiation is common. The aim was to investigate further lymphatic antigen expression, and to explore the relation of immunohistochemistry to morphological and clinical findings.Forty-nine angiosarcomas in tissue microarrays were analysed with D2-40 and antibodies to Prox-1 and vascular endothelial growth factor receptor (VEGFR)-3. D2-40 was positive in 53%, Prox-1 in 76%, and VEGFR-3 in 57%. Tumours with features attributable to lymphatic differentiation such as hobnail and kaposiform morphologies were more often positive with these markers, including a statistical association between D2-40 and hobnailing. Ten tumours had features suggestive of lymphatic differentiation, namely well-differentiated histology, interanastomosing channels devoid of red cells, prominent hobnailing, lymphoid aggregates, and multi-antigen expression of D2-40 (100%), Prox-1 (100%) and VEGFR-3 (60%), which might be deserving of the appellation lymphangiosarcoma. Nine were cutaneous scalp/facial tumours in elderly patients and one arose within chronic lymphoedema.Lymphatic differentiation is common in angiosarcoma, certain subsets show greater lymphatic differentiation than others, and lymphangiosarcoma may be defined pathologically, rather than clinically.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78689/1/j.1365-2559.2010.03484.x.pd

The application of immunocytochemistry to direct smears in the diagnosis of effusions

Metastatic malignancy represents a common cause of effusions. Immunocytochemistry (ICC) is useful in confirming malignancy and gaining insight into the site of origin. Cell blocks are commonly utilized for this purpose; nonetheless, when the malignant cells are sparse, they may not be represented in cell blocks thereby precluding immunophenotypic characterization. Thus, we sought to investigate the utility of direct smear preparations as a platform for ICC in the diagnosis of effusions. Air‐dried, unstained direct smears were prepared from 49 malignant effusions and 17 reactive effusions for comparison. ICC for EMA and MOC‐31 highlighted the tumor cells in 91 and 98% of the malignant effusions tested, respectively. EMA immunoreactivity was focally observed within the calretinin‐positive mesothelial cell population in 1 (6%) of the 17 reactive effusions. ICC for MOC‐31 was negative in all reactive effusions. Site‐specific immunomarkers were also evaluated. Immunoreactivity for Napsin‐A and TTF‐1 were observed in 78 and 67% of metastatic lung adenocarcinomas, respectively. ICC for PAX8 highlighted metastatic Müllerian and thyroid carcinomas in 100% of cases tested. CDX‐2 immunoreactivity was observed in 25, 60, and 100% of metastatic gastric, pancreatic, and colorectal adenocarcinomas, respectively. Positivity for p63 was observed in 75% of metastatic urothelial cell carcinomas and the one case of pulmonary squamous cell carcinoma examined. Calretinin ICC highlighted the tumor cells in both malignant mesothelioma cases tested as well as the benign mesothelial cells in the reactive effusions. In conclusion, direct smears represent an effective platform for the performance of ICC in the diagnosis of malignant effusions. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97537/1/22852_ftp.pd

Cluster analysis of immunohistochemical profiles delineates CK7, vimentin, S100A1 and C‐kit (CD117) as an optimal panel in the differential diagnosis of renal oncocytoma from its mimics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106819/1/j.1365-2559.2011.03753.x.pd

MaWGAN: a generative adversarial network to create synthetic data from datasets with missing data

The creation of synthetic data are important for a range of applications, for example, to anonymise sensitive datasets or to increase the volume of data in a dataset. When the target dataset has missing data, then it is common to just discard incomplete observations, even though this necessarily means some loss of information. However, when the proportion of missing data are large, discarding incomplete observations may not leave enough data to accurately estimate their joint distribution. Thus, there is a need for data synthesis methods capable of using datasets with missing data, to improve accuracy and, in more extreme cases, to make data synthesis possible. To achieve this, we propose a novel generative adversarial network (GAN) called MaWGAN (for masked Wasserstein GAN), which creates synthetic data directly from datasets with missing values. As with existing GAN approaches, the MaWGAN synthetic data generator generates samples from the full joint distribution. We introduce a novel methodology for comparing the generator output with the original data that does not require us to discard incomplete observations, based on a modification of the Wasserstein distance and easily implemented using masks generated from the pattern of missing data in the original dataset. Numerical experiments are used to demonstrate the superior performance of MaWGAN compared to (a) discarding incomplete observations before using a GAN, and (b) imputing missing values (using the GAIN algorithm) before using a GA

Review of additive manufactured tissue engineering scaffolds: relationship between geometry and performance

Material extrusion additive manufacturing has rapidly grown in use for tissue engineering research since its adoption in the year 2000. It has enabled researchers to produce scaffolds with intricate porous geometries that were not feasible with traditional manufacturing processes. Researchers can control the structural geometry through a wide range of customisable printing parameters and design choices including material, print path, temperature, and many other process parameters. Currently, the impact of these choices is not fully understood. This review focuses on how the position and orientation of extruded filaments, which sometimes referred to as the print path, lay-down pattern, or simply "scaffold design", affect scaffold properties and biological performance. By analysing trends across multiple studies, new understanding was developed on how filament position affects mechanical properties. Biological performance was also found to be affected by filament position, but a lack of consensus between studies indicates a need for further research and understanding. In most research studies, scaffold design was dictated by capabilities of additive manufacturing software rather than free-form design of structural geometry optimised for biological requirements. There is scope for much greater application of engineering innovation to additive manufacture novel geometries. To achieve this, better understanding of biological requirements is needed to enable the effective specification of ideal scaffold geometries

Polycystic ovary syndrome is associated with adverse mental health and neurodevelopmental outcomes

Context Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and subfertility, but the effects on mental health and child neurodevelopment are unclear. Objectives To determine if (1) there is an association between PCOS and psychiatric outcomes and (2) whether rates of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are higher in children of mothers with PCOS. Design Data were extracted from the Clinical Practice Research Datalink. Patients with PCOS were matched to two control sets (1:1) by age, body mass index, and primary care practice. Control set 2 was additionally matched on prior mental health status. Primary outcomes were the incidence of depression, anxiety, and bipolar disorder. Secondary outcomes were the prevalence of ADHD or ASD in the children. Results Eligible patients (16,986) were identified; 16,938 and 16,355 were matched to control sets 1 and 2, respectively. Compared with control set 1, baseline prevalence was 23.1% vs 19.3% for depression, 11.5% vs 9.3% for anxiety, and 3.2% vs 1.5% for bipolar disorder (P < 0.001). The hazard ratio for time to each endpoint was 1.26 (95% confidence interval 1.19 to 1.32), 1.20 (1.11 to 1.29), and 1.21 (1.03 to 1.42) for set 1 and 1.38 (1.30 to 1.45), 1.39 (1.29 to 1.51), and 1.44 (1.21 to 1.71) for set 2. The odds ratios for ASD and ADHD in children were 1.54 (1.12 to 2.11) and 1.64 (1.16 to 2.33) for set 1 and 1.76 (1.27 to 2.46) and 1.34 (0.96 to 1.89) for set 2. Conclusions PCOS is associated with psychiatric morbidity and increased risk of ADHD and ASD in their children. Screening for mental health disorders should be considered during assessment

Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer.

Cancer cells exhibit altered metabolism including aerobic glycolysis that channels several glycolytic intermediates into de novo purine biosynthetic pathway. We discovered increased expression of phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas. Transcript analyses from next-generation RNA sequencing and gene expression profiling studies suggested that PPAT and PAICS can serve as prognostic biomarkers for aggressive lung adenocarcinoma. Immunohistochemical analysis of PAICS performed on tissue microarrays showed increased expression with disease progression and was significantly associated with poor prognosis. Through gene knockdown and over-expression studies we demonstrate that altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Furthermore we identified genomic amplification and aneuploidy of the divergently transcribed PPAT-PAICS genomic region in a subset of lung cancers. We also present evidence for regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-Diazo-5-oxo-L-norleucine (DON) blocked glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity. In summary, this study reveals the regulatory mechanisms by which purine biosynthetic pathway enzymes PPAT and PAICS, and pyruvate kinase activity is increased and exposes an existing metabolic vulnerability in lung cancer cells that can be explored for pharmacological intervention

Epidermal Growth Factor Receptor Expression and Mutational Analysis in Synovial Sarcomas and Malignant Peripheral Nerve Sheath Tumors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140003/1/onco0459.pd